Estrogen fix.

Top Line: Think you understand breast cancer prevention? Think again.

The Studies: We’ve known for nearly three decades that prophylactic estrogen deprivation can help prevent breast cancer incidence in high-risk populations. Kicker is these prevented cancers are typically the most indolent ones, meaning lots and lots of side effects are being doled out, even with baby tam, without saving any lives. This useful review helps us put into context the results of two huge randomized trials exploring different approaches to meaningful breast cancer prevention. First up, the Women's Health Initiative Dietary Modification trial that randomized, between 1993-1998, 48,835 post-menopausal women with no history of breast cancer to +/- an 8.5-year program aimed to reduce dietary fats and increase vegetable, fruit, and whole grain daily intake. Beyond significant weight loss—which is all most women will need to hear—the intervention group achieved a significantly lower incidence of specifically ER+/PR- breast cancer (HR 0.77) that translated to a lower risk of breast cancer death (HR 0.79). Second up, another Women’s Health Initiative trial that randomized, again between 1993-1998, 10,739 post-menopausal post-hysterectomy women to +/- daily conjugated equine estrogen—yep, that tried and true estrogen supplement isolated for the first time in 1942. Granted the goal was to measure its effects on a whole cadre of prespecified chronic diseases, only one of which was breast cancer, the estrogen arm indeed achieved a significantly lower incidence of ER+/PR- breast cancer (HR 0.44) that translated again to a lower risk of breast cancer death (HR 0.60). Now, don’t forget this is in stark contrast to the notorious parallel trial of estrogen + progestin supplementation in postmenopausal women with a uterus that virtually shut down the hormone replacement game over night with its publication in 2002. That is all to say, estrogen may have long been taking unmerited heat due to its frequent association with its more nefarious cousin progesterone.

TBL: Low-fat diets and conjugated equine estrogens can slash the risk of clinically-significant breast cancer and even reduce breast cancer mortality by 20-40% and deserve further study as less morbid and potentially more effective prevention strategies than that of dreaded hormone deprivation. | Chlebowski, JCO Pract Oncol 2021